Phosphorus oxychloride → 5-Chloro-7-{5-[1-(tetrahydro pyran-4-yl) piperidin-4-yl]-[1,3,4]oxadiazol-2-yl}-2,3-dihydro benzofuran-4-yl amine

HRID 1523736노트

반응식

HRID 1523736 반응식
[O:1]1[CH2:6][CH2:5][CH:4]([N:7]2[CH2:12][CH2:11][CH:10]([C:13]([OH:15])=O)[CH2:9][CH2:8]2)[CH2:3][CH2:2]1.P(Cl)(Cl)(Cl)=O.[NH2:21][C:22]1[C:27]2[CH2:28][CH2:29][O:30][C:26]=2[C:25]([C:31]([NH:33][NH2:34])=O)=[CH:24][C:23]=1[Cl:35]>>[Cl:35][C:23]1[CH:24]=[C:25]([C:31]2[O:15][C:13]([CH:10]3[CH2:9][CH2:8][N:7]([CH:4]4[CH2:3][CH2:2][O:1][CH2:6][CH2:5]4)[CH2:12][CH2:11]3)=[N:34][N:33]=2)[C:26]2[O:30][CH2:29][CH2:28][C:27]=2[C:22]=1[NH2:21]

참가 물질

4

반응물 3

HCID 24813Phosphorus oxychlorideHCID 252204681-Tetrahydro-2H-pyran-4-ylpiperidine-4-carboxylic acidHCID 867249204-Amino-5-chloro-2,3-dihydro benzofuran-7-carboxylic acid hydrazide

생성물 1

HCID 715347815-Chloro-7-{5-[1-(tetrahydro pyran-4-yl) piperidin-4-yl]-[1,3,4]oxadiazol-2-yl}-2,3-dihydro benzofuran-4-yl amine수율 13.1%

실험 절차

To 1-(tetrahydro pyran-4-yl) piperidine-4-carboxylic acid (168.2 mg, 0.58 mmol) was added phosphoryl chloride (1.76 mL). The mixture was stirred for 15 minutes and 4-amino-5-chloro-2,3-dihydro benzofuran-7-carboxylic acid hydrazide (101.2 mg, 0.0.44 mmol, obtained in preparation 3) was added. The reaction mixture was gradually heated to reflux for 2 hours. The reaction mixture was cooled to room temperature, triturated with hexanes (2×20 mL) and the crude mass was basified with aqueous sodium bicarbonate solution. The basified mixture was extracted with 10% methanol in dichloromethane. The organic layer was dried over anhydrous sodium sulphate and the solvent was removed under reduced pressure. The residual mass was purified by silica gel column to obtain 5-chloro-7-{5-[1-(tetrahydro pyran-4-yl) piperidin-4-yl]-[1,3,4]oxadiazol-2-yl}-2,3-dihydro benzofuran-4-yl amine (23.5 mg).

후처리

  1. temperatureThe reaction mixture was gradually heated
  2. temperatureto reflux for 2 hours
  3. customtriturated with hexanes (2×20 mL)
  4. extractionThe basified mixture was extracted with 10% methanol in dichloromethane
  5. dry with materialThe organic layer was dried over anhydrous sodium sulphate
  6. customthe solvent was removed under reduced pressure
  7. customThe residual mass was purified by silica gel column

출처 및 근거

ORD 기록
ord-f4353d00a6104b0b82ea430db0cf99d7
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09079894B2

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